POS0513 SAFETY OF FILGOTINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: ANALYSIS OF LYMPHOCYTES IN THE LONG-TERM EXTENSION FINCH 4 STUDY
Authors: J. E. Gottenberg, G. R. Burmester, K. Van Beneden, C. Watson, I. Seghers, V. Rajendran, L. Dagna, M. H. Buch
Journal: Annals of the Rheumatic Diseases (2022)

Background Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor approved for the treatment of moderate to severe rheumatoid arthritis (RA) in patients (pts) with an inadequate response to disease-modifying antirheumatic drugs. 1 In a pooled analysis of Phase 3 FINCH 1–3 studies of FIL in RA, median lymphocyte levels were relatively stable over 1 year with lymphocyte decreases observed in individual FIL-treated pts. Lymphocyte levels should be monitored. 1 Objectives To assess the effect of FIL on lymphocyte levels and lymphopenia in the FINCH 4 long-term extension (LTE) study in RA. Methods Safety data of FIL 100 mg (FIL100) and 200 mg (FIL200) from LTE baseline to data cut off (01 June 2020) are reported overall and by prior FIL exposure for pts who received ≥1 FIL dose in FINCH 4 ( NCT03025308 ; adults with RA who had completed FINCH 1/2/3). Adverse events (AEs) of lymphopenia were graded based on clinical severity; laboratory abnormalities (decreased lymphocytes) were graded per Common Terminology Criteria for Adverse Events v4.03 (CTCAE). Frequencies of both measures and exposure-adjusted incidence rates (EAIRs) of AEs are reported. Median lymphocyte levels are reported to LTE Week 48. Results The safety analysis set included 2729 pts (FIL200: n=1530; FIL100: n=1199). Of these, 75.4% (n=2058) had prior FIL exposure in FINCH 1/2/3. Median FIL exposure to LTE Week 48 was 600 (FIL200: 696; FIL100: 533) days. In both treatment groups, median laboratory lymphocyte levels remained relatively stable to LTE Week 48 for pts with prior FIL exposure. Pts without prior exposure had numerically higher median lymphocyte levels at LTE baseline vs pts with prior exposure (Figure 1). These decreased over time, but medians remained within normal range. The frequency and EAIR of graded decreases in laboratory lymphocyte levels were higher with FIL200 vs FIL100 (Table 1); incidence was slightly higher in pts with vs without prior FIL exposure, with the difference most apparent for Grade 2 decreases. Table 1. Frequencies of treatment-emergent laboratory decreases in lymphocytes Prior FIL exposure No prior FIL exposure Overall Total FIL200 FIL100 FIL200 FIL100 FIL200 FIL100 (N=2729) (n=1195) (n=863) (n=335) (n=336) (n=1530) (n=1199) Decreased lymphocytes 228 (19.1) 125 (14.5) 41 (12.3) 40 (12.0) 269 (17.6) 165 (13.8) 434 (16.0) (any grade), n (% ) Grade 1 48 (4.0) 35 (4.1) 14 (4.2) 7 (2.1) 62 (4.1) 42 (3.5) 104 (3.8) Grade 2 159 (13.3) 82 (9.5) 21 (6.3) 26 (7.8) 180 (11.8) 108 (9.1) 288 (10.6) Grade 3 21 (1.8) 8 (0.9) 6 (1.8) 7 (2.1) 27 (1.8) 15 (1.3) 42 (1.5) Grade 4 0 0 0 0 0 0 0 A treatment-emergent laboratory decrease in lymphocytes was defined as an increase of ≥1 toxicity grade from baseline at any time post-baseline up to and including the date of last study drug dose + 30 days. Severity grades were defined per CTCAE (lower limit of normal: &lt;0.8 × 10 9 /L [Grade 1]; &lt;0.8–0.5 × 10 9 /L [2]; &lt;0.5–0.2 × 10 9 /L [3]; &lt;0.2 × 10 9 /L [4]). Figure 1. Of all pts receiving FIL, 43 (1.6%) reported a lymphopenia AE; frequencies and EAIRs of lymphopenia AEs were slightly higher with FIL200 (1.9%; EAIR [95% CI]: 1.2 [0.9–1.8]) vs FIL100 (1.2%; 0.8 [0.4–1.3]). Most were Grade 1 or 2 in severity. Grade 3 lymphopenia AEs occurred in 4 (0.3%) vs 1 (&lt;0.1%) pts receiving FIL200 vs FIL100. There were no Grade 4 AEs in either group. No serious AEs of lymphopenia or treatment discontinuations due to lymphopenia were reported. In total, 8 (0.3%) pts interrupted study treatment due to lymphopenia. Infection rates, but not serious infections, were slightly higher for pts with lymphopenia, however no relationship between lymphopenia severity and infection AE grade was seen. Conclusion In FINCH 4, lymphopenia AEs were infrequent but numerically greater with FIL200 vs FIL100, suggesting a dose–response relationship. While exposure at either dose may be associated with decreased lymphocytes, median lymphocyte levels were comparable in both groups and all remained within normal range at LTE Week 48, similar to observations in FINCH 1–3. References [1]Filgotinib SmPC and Jyseleca EPAR, 2020. Available at: https://www.ema.europa.eu/en Acknowledgements The authors would like to acknowledge Nadia Verbruggen and Pieter-Jan Stiers for providing statistical analysis support. This study was co-funded by Galapagos NV (Mechelen, Belgium) and Gilead Sciences, Inc. (Foster City, CA, USA). Medical writing support was provided by Kristian Clausen, MPH, CMPP (Aspire Scientific Ltd, Bollington, UK), and funded by Galapagos NV. Disclosure of Interests Jacques-Eric Gottenberg Consultant of: AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, and Pfizer, Grant/research support from: Bristol Myers Squibb, and Pfizer, Gerd Rüdiger Burmester Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Lilly, MSD, Pfizer, Roche, and Sanofi, Katrien Van Beneden Shareholder of: Galapagos NV, Employee of: Galapagos NV, Chris Watson Shareholder of: Galapagos Biotech Ltd, Employee of: Galapagos Biotech Ltd, Ineke Seghers Employee of: Galapagos NV, Vijay Rajendran Employee of: Galapagos NV, Lorenzo Dagna Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and Swedish Orphan Biovitrium (SOBI), Grant/research support from: Bristol Myers Squibb, Celltrion, Kiniksa Pharmaceuticals, Pfizer, and Swedish Orphan Biovitrium (SOBI), Maya H Buch Speakers bureau: Speaker fees paid to host institution by AbbVie, Consultant of: Consultant honoraria paid to host institution by AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer.